The objectives of this project are to 1) use both molecular and classical approaches to investigate pathogen-arthropod interactions of vector-borne diseases of human importance in the United States, and 2) examine basic biological questions concerning the behavior of ticks and fleas that influence their ability to transmit infectious agents. In this project, we have already 1) developed DNA hybridization probes to detect Yersinia pestis, the causative agent of plague, in experimentally infected fleas and rodents, and 2) developed a recombinant vaccine that protected mice when challenged with virulent Y. pestis. More recently we examined the ability of soft ticks to become infected with Y. pestis and in some cases, maintain the infection for up to one year, demonstrating the potential for some species of soft ticks to maintain and reservoir this bacterium in nature. A final project with Y. pestis is currently underway to use the polymerase chain reaction (PCR) to detect Y. pestis in Xenopsylla cheopis, the classical flea vector of urban plague, which we have colonized at RML. We have recently completed the description of a new species of Argas tick from California and determined its life cycle and potential as a vector to transmit an Orbivirus (Reoviridae) to humans. Most of our current and future efforts will focus on novel isolates of relapsing fever Borrelia from human patients in the western United States and explore their molecular basis for antigenic variation.